Nearly two-thirds of the US population is either clinically overweight or obese and almost 10% of the population has adult-onset diabetes. Obesity and diabetes are central elements of a cluster of pathologies collectively referred to as metabolic syndrome. Our Center of Biomedical Research Excellence (COBRE) at the Pennington Biomedical Research Center was established to enhance research on metabolic disease by increasing the number of extramurally-funded faculty devoted to this research and expanding the scientific infrastructure needed for its conduct. During Phases I and II of our COBRE, our Center has provided support to 15 junior faculty members who have obtained 14 NIH grants (7 RO1, 2 RO3, 1 R21, 1 R56, 2 R41, 1 R43) and 5 research grants from the ADA. In addition, the research infrastructure has been significantly improved by (1) enhancement of the Genomics Core through hardware upgrades and addition of Bioinformatics support to the core's activities, and (2) establishment of an outstanding, well equipped Cell Biology and Bio-imaging Core that has provided high levels of expertise and service to institutional faculty and Project PIs supported by our COBRE. The Specific Aims of our COBRE in Phase III are to further expand the critical mass of productive investigators engaged in metabolic disease research by (a) maintaining the highly effective mentoring culture we have built and refined during the first two phases of our Center; (b) identifying, mentoring, and retaining our most talented, well-trained junior scientists emerging from our institutional training grants; (c) continuing to enhance the growth of our scientific cores by leveraging institutional support to sustain their strong positive impact on the success of Center scientists, and (4) sustaining a collaborative multidisciplinary research environment by providing support for research pilot projects that are critical to obtaining new extramural support and sustaining the Center's basic and translational research activities.